Small non-coding microRNAs (miRNAs, miRs) with a length of approximately 22 nucleotides are important post-transcriptional regulators of numerous human genes. MiRNAs modulate the expression of tumor suppressor genes as well as oncogenes [1-3]. In breast cancer (BC), emerging evidence suggests a potential role for deregulated miRNAs as modulators of carcinogenesis, proliferation, apoptosis and drug-resistance, respectively [4]. Most data exist for tumor tissue or breast cancer cell line-based miRNA expression profiles [5, 6]. However, there are numerous hypotheses for a pivotal role of miRNAs in intercellular communication [7, 8] partially based on the leakage of miRNAs in circulation [9] as well as by active and passive export mechanisms, respectively [9]. Recent studies documented the feasibility to detect stable miRNAs in serum and plasma. This opened the field for these circulating miRNAs as potential novel biomarkers in BC for early detection but also outcome prediction [10-13]. Our extensive literature research revealed the following nine miRNAs as actually relevant in BC, especially as potential blood based biomarker in discrimination BC from healthy controls or as predictors in therapy response (Table 1). For example, high expression serum levels of miR-10b, 34a and 155 were associated with primary metastatic BC (p<0.05) and high miR-34a levels correlated with an advanced stage of disease (p=0.01) [11]. Additional data revealed a strong correlation between serum miR-122 and miR-375 levels and neoadjuvant chemotherapy response in locally advanced BC [14]. Overexpression of miR-21 in BC tissue as well in blood based studies has a relevant oncogenic role by promoting invasion, proliferation and metastases and poor prognosis in BC patients [10, 15, 16]. Emerged studies showed up-regulated miR-125b serum levels in BC patients as an innovative serum biomarker for discrimination BC patients from healthy controls and to predict chemotherapeutic resistance [22, 23]. Other studies indicated miR-155 and miR-195 as promising diagnostic targets, while miR-155 is also discussed as a potential therapeutic target in BC [13, 17-20]. The role of miR-200 family in blocking tumor angiogenesis by inhibition epithelial-mesenchymal transition represents a potential relevant therapeutic predictive parameter in BC therapy [21, 22]. Most interestingly, in one study higher expression levels of miR-200b and miR-200c were observed in serum from circulating tumor cells (CTC)-positive metastatic BC patients compared to CTC-negative patients and promised miR-200b and miR-200c as an indicator for CTC-status and a prognostic marker in metastatic BC [23]. In regard of BC detection and discrimination from healthy controls miR-451 in combination with miR-145 were identified as the best potential circulating biomarker [24].
So far, urine, as an easy approachable compartment and a non-invasive source for circulating miRNAs, has not been tested in the setting of BC while current studies suggest a high potential of urinary miRNAs in urologic cancers [9].